Dofetilide Dose Reductions and Discontinuation in Obese Compared with Nonobese Patients

Dofetilide is an antiarrhythmic agent and primarily eliminated renally. Initial dosing is determined by creatinine clearance, calculated by total body weight in the Cockcroft-Gault equation. To date, there is no evidence comparing the dosing of dofetilide in obese versus nonobese patients. We conducted a retrospective review of 217 adults admitted for dofetilide loading to evaluate the tolerability of dofetilide in obese versus nonobese patients. The rate of dose adjustments, including dose reductions and discontinuations, was compared between obese versus nonobese patients in unadjusted and adjusted analyses. Electrocardiograms were collected throughout the loading period, and calculation of QT intervals was performed. Obese patients did not have a significantly higher frequency of dose adjustments compared with nonobese patients (51.5% vs. 44.8%, P = 0.33). Using total body weight to determine starting doses was associated with great odds of dose adjustments compared with ideal body weight (OR 3.69, P = 0.002) and adjusted body weight (OR 4.46, P = 0.02). Men required significantly fewer dose adjustments compared with women on multivariate analysis (OR 0.53, P = 0.03). Obesity is not associated with an increase in the rate of dose adjustments. Total body weight should be used with caution to calculate initial doses of dofetilide in women because it may lead to a higher rate of dose adjustments compared with ideal body weight. Additional studies are needed to confirm the optimal method for selecting starting doses of dofetilide in women, particularly those with a body mass index of ≥30.